Beretta, Lorenzo, Barturen, Guillermo, Vigone, Barbara, Bellocchi, Chiara, Hunzelmann, Nicolas, De Langhe, Ellen, Cervera, Ricard, Gerosa, Maria, Kovacs, Laszlo, Ortega Castro, Rafaela, Almeida, Isabel, Cornec, Divi, Chizzolini, Carlo, Pers, Jacques-Olivier, Makowska, Zuzanna, Lesche, Ralf, Kerick, Martin, Eugenia Alarcon-Riquelme, Marta and Martin, Javier ORCID: 0000-0002-2202-0622 (2020). Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients. Ann. Rheum. Dis., 79 (9). S. 1218 - 1227. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2060

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Abstract

Objectives The analysis of annotated transcripts from genome-wide expression studies may help to understand the pathogenesis of complex diseases, such as systemic sclerosis (SSc). We performed a whole blood (WB) transcriptome analysis on RNA collected in the context of the European PRECISESADS project, aiming at characterising the pathways that differentiate SSc from controls and that are reproducible in geographically diverse populations. Methods Samples from 162 patients and 252 controls were collected in RNA stabilisers. Cases and controls were divided into a discovery (n=79+163; Southern Europe) and validation cohort (n=83+89; Central-Western Europe). RNA sequencing was performed by an Illumina assay. Functional annotations of Reactome pathways were performed with the Functional Analysis of Individual Microarray Expression (FAIME) algorithm. In parallel, immunophenotyping of 28 circulating cell populations was performed. We tested the presence of differentially expressed genes/pathways and the correlation between absolute cell counts and RNA transcripts/FAIME scores in regression models. Results significant in both populations were considered as replicated. Results Overall, 15 224 genes and 1277 functional pathways were available; of these, 99 and 225 were significant in both sets. Among replicated pathways, we found a deregulation in type-I interferon, Toll-like receptor cascade, tumour suppressor p53 protein function, platelet degranulation and activation. RNA transcripts or FAIME scores were jointly correlated with cell subtypes with strong geographical differences; neutrophils were the major determinant of gene expression in SSc-WB samples. Conclusions We discovered a set of differentially expressed genes/pathways validated in two independent sets of patients with SSc, highlighting a number of deregulated processes that have relevance for the pathogenesis of autoimmunity and SSc.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Beretta, LorenzoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barturen, GuillermoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vigone, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bellocchi, ChiaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hunzelmann, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Langhe, EllenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cervera, RicardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerosa, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kovacs, LaszloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortega Castro, RafaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Almeida, IsabelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cornec, DiviUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chizzolini, CarloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pers, Jacques-OlivierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Makowska, ZuzannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lesche, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerick, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eugenia Alarcon-Riquelme, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, JavierUNSPECIFIEDorcid.org/0000-0002-2202-0622UNSPECIFIED
URN: urn:nbn:de:hbz:38-321658
DOI: 10.1136/annrheumdis-2020-217116
Journal or Publication Title: Ann. Rheum. Dis.
Volume: 79
Number: 9
Page Range: S. 1218 - 1227
Date: 2020
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1468-2060
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENE-EXPRESSION; RNA-SEQ; PATHOGENESIS; DISEASEMultiple languages
RheumatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32165

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